tbuckley/cabot-search huggingface dataset:
Association of Ischemic and Bleeding Events With Mortality Among Patients in Sweden With Recent Acute Myocardial Infarction Receiving Antithrombotic Therapy
Authors: Moa Simonsson, Joakim Alfredsson, Karolina Szummer, Tomas Jernberg, Peter Ueda
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Antithrombotic treatment after myocardial infarction (MI) should be individualized based on the patient's risk of ischemic and bleeding events. Uncertainty remains regarding the relative prognostic importance of the 2 types of events, and further study would be useful. <h3>Objectives</h3> To compare the association of ischemic vs bleeding events with mortality in patients with a recent MI and assess whether the relative mortality risk for the 2 types of events has changed over the past 2 decades. <h3>Design, Setting, and Participants</h3> A cohort study based on nationwide registers in Sweden, 2012-2017, was conducted. Data were analyzed between July 2021 and May 2022. Patients with MI who were discharged alive with antithrombotic therapy (antiplatelet therapy or oral anticoagulation) were included in the analysis. <h3>Main Outcomes and Measures</h3> The incidence of a first ischemic event (hospitalization for MI or ischemic stroke) or bleeding event (hospitalization with bleeding) up to 1 year after discharge and the mortality risk up to 1 year after each type of event were assessed. Cox proportional hazards regression models were used to estimate adjusted hazard ratios (aHRs) for 1-year mortality after an ischemic and bleeding event vs no event, and after an ischemic vs bleeding event. Adjusted HRs for mortality after ischemic vs bleeding events were compared among patients discharged in 1997-2000, 2001-2011, and 2012-2017. <h3>Results</h3> Of 86 736 patients discharged after MI in 2012-2017 (median age, 71 [IQR, 62-80] years; 57 287 [66.0%] men), 4039 individuals experienced a first ischemic event (5.7 per 100 person-years) and 3399 experienced a first bleeding event (4.8 per 100 person-years). The mortality rate was 46.2 per 100 person-years after an ischemic event and 27.1 per 100 person-years after a bleeding event. The aHR for 1-year mortality vs no event was 4.16 (95% CI, 3.91-4.43) after an ischemic event and 3.43 (95% CI, 3.17-3.71) after a bleeding event. When the 2 types of events were compared, the aHR was 1.27 (95% CI, 1.15-1.40) for an ischemic vs bleeding event. There was no statistically significant difference in the aHR of an ischemic vs bleeding event in 1997-2000, 2001-2011, and 2012-2017. <h3>Conclusions and Relevance</h3> In this nationwide cohort study of patients with a recent MI, postdischarge ischemic events were more common and associated with higher mortality risk compared with bleeding events.
A senescence stress secretome is a hallmark of therapy-related myeloid neoplasm stromal tissue occurring soon after cytotoxic exposure
Authors: Monika M. Kutyna, Chung Hoow Kok, Yoon Lim, Elizabeth Ngoc Hoa Tran, David Campbell, Sharon Paton, Chloe Thompson-Peach, Kelly Lim, Dimitrios Cakouros, Agnes Arthur, Timothy Hughes, Sharad Kumar, Daniel Thomas, Stan Gronthos, Devendra K. Hiwase
Journal: Leukemia (2022)

Therapy-related myeloid neoplasm (tMN) is considered a direct consequence of DNA damage in hematopoietic stem cells. Despite increasing recognition that altered stroma can also drive leukemogenesis, the functional biology of the tMN microenvironment remains unknown. We performed multiomic (transcriptome, DNA damage response, cytokine secretome and functional profiling) characterization of bone marrow stromal cells from tMN patients. Critically, we also compared (i) patients with myeloid neoplasm and another cancer but without cytotoxic exposure, (ii) typical primary myeloid neoplasm, and (iii) age-matched controls to decipher the microenvironmental changes induced by cytotoxics vs. neoplasia. Strikingly, tMN exhibited a profoundly senescent phenotype with induction of CDKN1A and β-Galactosidase, defective phenotype, and proliferation. Moreover, tMN stroma showed delayed DNA repair and defective adipogenesis. Despite their dormant state, tMN stromal cells were metabolically highly active with a switch toward glycolysis and secreted multiple pro-inflammatory cytokines indicative of a senescent-secretory phenotype that inhibited adipogenesis. Critically, senolytics not only eliminated dormant cells, but also restored adipogenesis. Finally, sequential patient sampling showed senescence phenotypes are induced within months of cytotoxic exposure, well prior to the onset of secondary cancer. Our data underscores a role of senescence in the pathogenesis of tMN and provide a valuable resource for future therapeutics.
Recent advances in therapeutic strategies for triple-negative breast cancer
Authors: Yun Li, Huajun Zhang, Yulia Merkher, Lin Chen, Na Liu, Sergey Leonov, Yongheng Chen
Journal: Journal of Hematology & Oncology (2022)

Abstract Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer (BC) with a poor prognosis. Current treatment options are limited to surgery, adjuvant chemotherapy and radiotherapy; however, a proportion of patients have missed the surgical window at the time of diagnosis. TNBC is a highly heterogeneous cancer with specific mutations and aberrant activation of signaling pathways. Hence, targeted therapies, such as those targeting DNA repair pathways, androgen receptor signaling pathways, and kinases, represent promising treatment options against TNBC. In addition, immunotherapy has also been demonstrated to improve overall survival and response in TNBC. In this review, we summarize recent key advances in therapeutic strategies based on molecular subtypes in TNBC.
Learning from Online Video Education (LOVE) improves confidence in fertility treatments: a randomized controlled trial
Authors: Amanda Adeleye, Katrina Cruz, Marcelle I. Cedars, Lauri Pasch, Heather Huddleston
Journal: npj Digital Medicine (2022)

Fertility treatments like in vitro fertilization (IVF) or oocyte cryopreservation (OC) require the daily use of injectable gonadotropins and has been associated with treatment burden and attrition from fertility treatment. We conducted a randomized clinical trial to determine (1) whether educational videos about fertility medications improved infertility self-efficacy scale (ISES), fertility quality of life treatment (FertiQoL-T), and Perceived stress scale (PSS) scores and (2) if such videos improved confidence and reduced medication errors during a first ovarian stimulation cycle. Participants were given access to an online portal with randomized access to either placebo control videos focused on an orientation to IVF or experimental videos that reviewed the preparation and administration of medications used during ovarian stimulation in addition to the placebo videos. Participants completed pre and post-treatment questionnaires. 368 patients enrolled and 257 participants completed the study. There were no differences in ISES, FertiQoL-T or PSS scores between the two groups in an intention-to-treat (p = 0.18, 0.72, and 0.92, respectively) or per-protocol analysis (p = 0.11, 0.38, and 0.37, respectively). In the per protocol analysis, participants who watched experimental videos were four-fold more likely to report confidence administering medications OR 4.70 (95% CI: 2.10, 11.1; p < 0.01) and were 63% less likely to make medication errors OR 0.37 (95% CI: 0.14, 0.90; p = 0.03). Participants had similar likelihoods of rating videos as helpful and recommending videos to others (p = 0.06 and 0.3, respectively). Educational videos about fertility medications may not influence psychological well-being but might improve confidence in medication administration and reduce medication errors. Trial registration number: NCT02979990.
Corneal fibrosis abrogation by a localized AAV-mediated inhibitor of differentiation 3 (Id3) gene therapy in rabbit eyes in vivo
Authors: Suneel Gupta, Michael K. Fink, Duraisamy Kempuraj, Nishant R. Sinha, Lynn M. Martin, Landon M. Keele, Prashant R. Sinha, Elizabeth A. Giuliano, Nathan P. Hesemann, Sudhanshu P. Raikwar, Shyam S. Chaurasia, Rajiv R. Mohan
Journal: Molecular Therapy (2022)

(Molecular Therapy 30, 3257–3269; October 2022) In the originally published version of this article, the authors missed citing Dr. Sudhanshu Raikwar’s contribution in the manuscript of cloning Id3 gene into AAV plasmid (pTRUF11) while he was working in Dr. Mohan’s lab. To correct this error, all co-authors have agreed to include Sudhanshu Raikwar as a co-author. The authors apologize for this error, and this error has been corrected online. Corneal fibrosis abrogation by a localized AAV-mediated inhibitor of differentiation 3 (Id3) gene therapy in rabbit eyes in vivoGupta et al.Molecular TherapyJuly 1, 2022In BriefOur results indicate that localized AAV5-Id3 delivery in stroma caused no clinically relevant ocular symptoms or corneal cellular toxicity in rabbit eyes. Full-Text PDF
Task Autonomy of a Flexible Endoscopic System for Laser-Assisted Surgery
Authors: Hangjie Mo, Xiaojian Li, Bo Ouyang, Ge Fang, Yuanjun Jia
Journal: Cyborg and Bionic Systems (2022)

Laser beam steering has been widely studied for the automation of surgery. Currently, flexible instruments for laser surgery are operated entirely by surgeons, which keeps the automation of endoluminal surgery at the initial level. This paper introduces the design of a new workflow that enables the task autonomy of laser-assisted surgery in constrained environments such as the gastrointestinal (GI) tract with a flexible continuum robotic system. Unlike current, laser steering systems driven by piezoelectric require the use of high voltage and are risky. This paper describes a tendon-driven 2 mm diameter flexible manipulator integrated with an endoscope to steer the laser beam. By separating its motion from the total endoscopic system, the designed flexible manipulator can automatically manipulate the laser beam. After the surgical site is searched by the surgeon with a master/slave control, a population-based model-free control method is applied for the flexible manipulator to achieve accurate laser beam steering while overcoming the noise from the visual feedback and disturbances from environment during operation. Simulations and experiments are performed with the system and control methods to demonstrate the proposed framework in a simulated constrained environment.
Air Pollution–Related Neurotoxicity Across the Life Span
Authors: Deborah A. Cory-Slechta, Alyssa Merrill, Marissa Sobolewski
Journal: The Annual Review of Pharmacology and Toxicology (2022)

Air pollution is a complex mixture of gases and particulate matter, with adsorbed organic and inorganic contaminants, to which exposure is lifelong. Epidemiological studies increasingly associate air pollution with multiple neurodevelopmental disorders and neurodegenerative diseases, findings supported by experimental animal models. This breadth of neurotoxicity across these central nervous system diseases and disorders likely reflects shared vulnerability of their inflammatory and oxidative stress–based mechanisms and a corresponding ability to produce brain metal dyshomeo-stasis. Future research to define the responsible contaminants of air pollution underlying this neurotoxicity is critical to understanding mechanisms of these diseases and disorders and protecting public health.
Pharmacological Induction of Granulocyte Cell Death as Therapeutic Strategy
Authors: Thomas Kaufmann, Hans-Uwe Simon
Journal: The Annual Review of Pharmacology and Toxicology (2022)

Apoptosis is central for the maintenance of health. In the immune system, apoptosis guarantees proper development of immune cells and shutdown of immune reactions by the coordinated elimination of activated immune cells. Limitation of the life span of granulocytes is important, as overactivation of these cells is associated with chronic inflammation and collateral tissue damage. Consequently, targeted induction of granulocyte apoptosis may be beneficial in the course of respective immune disorders. Anti-inflammatory drugs such as glucocorticoids and monoclonal antibodies against IL-5Rα exert their function in part by triggering eosinophil apoptosis. Agonistic antibodies targeting Siglec-8 or death receptors are tested (pre)clinically. Moreover, a new class of inhibitors targeting antiapoptotic BCL-2 proteins shows great promise for anticancer treatments. Because of their specificity and tolerable side effects, these so-called BH3 mimetics may be worthwhile to evaluate in inflammatory disorders. Here, we review past and recent data on pharmacological apoptosis induction of granulocytes and highlight respective therapeutic potential.
Association Between Device-Measured Physical Activity and Incident Heart Failure: A Prospective Cohort Study of 94 739 UK Biobank Participants
Authors: Frederick K. Ho, Ziyi Zhou, Fanny Petermann-Rocha, Solange Para-Soto, Jirapitcha Boonpor, Paul Welsh, Jason M.R. Gill, Stuart R. Gray, Naveed Sattar, Jill P. Pell, Carlos Celis-Morales
Journal: Circulation (2022)

Background: Studies of objectively measured physical activity (PA) have investigated acute cardiovascular outcomes but not heart failure (HF), an emerging chronic condition. This study aimed to investigate the dose-response relationship between device-measured PA and HF by intensity of PA. Methods: This was a prospective cohort study of 94 739 UK Biobank participants who had device-measured PA in 2013 to 2015 and were free from myocardial infarction and HF. PA was measured with a wrist-worn accelerometer, and time spent on light-, moderate-, and vigorous-intensity PA was extracted. Incident HF was ascertained from linked hospital and death records. Cox proportional hazard models with cubic penalized splines were used to study the associations, which were adjusted for sociodemographic and lifestyle factors. Competing risk was handled with cause-specific hazard ratios. Results: The overall incidence of HF was 98.5 per 10 000 person-years over a median 6.1 years of follow-up. Compared with participants who undertook no moderate- to vigorous-intensity PA, those who performed 150 to 300 min/wk of moderate-intensity PA (hazard ratio, 0.37 [95% CI, 0.34–0.41]) and 75 to 150 min/wk of vigorous-intensity PA (hazard ratio, 0.34 [95% CI, 0.25–0.46]) were at lower HF risk. The association between vigorous-intensity PA and HF was reverse-J shaped with a potentially lower risk reduction above 150 min/wk. Conclusions: Device-measured PA, especially moderate-intensity PA, was associated with a lower risk of HF. Current vigorous-intensity PA recommendations should be encouraged but not increased. In contrast, increasing moderate-intensity PA may be beneficial even among those meeting current recommendations.
A Dancing Trapped Intracardiac Thrombus
Authors: Aurélien Vallee, Thomas Lemann, Laurent Savale, Julien Guihaire, Olaf Mercier
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"A Dancing Trapped Intracardiac Thrombus." American Journal of Respiratory and Critical Care Medicine, 206(11), pp. 1405–1407
CircRNA-CREIT inhibits stress granule assembly and overcomes doxorubicin resistance in TNBC by destabilizing PKR
Authors: Xiaolong Wang, Tong Chen, Chen Li, Wenhao Li, Xianyong Zhou, Yaming Li, Dan Luo, Ning Zhang, Bing Chen, Lijuan Wang, Wenjing Zhao, Shanji Fu, Qifeng Yang
Journal: Journal of Hematology & Oncology (2022)

Circular RNAs (circRNAs) represent a novel type of regulatory RNA characterized by high evolutionary conservation and stability. CircRNAs are expected to be potential diagnostic biomarkers and therapeutic targets for a variety of malignancies. However, the regulatory functions and underlying mechanisms of circRNAs in triple-negative breast cancer (TNBC) are largely unknown.
Correction: IgM antibodies derived from memory B cells are potent cross-variant neutralizers of SARS-CoV-2
Authors: Malika Hale, Jason Netland, Yu Chen, Christopher D. Thouvenel, Katherine Nabel Smith, Lucille M. Rich, Elizabeth R. Vanderwall, Marcos C. Miranda, Julie Eggenberger, Linhui Hao, Michael J. Watson, Charles C. Mundorff, Lauren B. Rodda, Neil P. King, Miklos Guttman, Michael Gale, Jonathan Abraham, Jason S. Debley, Marion Pepper, David J. Rawlings
Journal: The Journal of Experimental Medicine (2022)
Effect of statin therapy on muscle symptoms: an individual participant data meta-analysis of large-scale, randomised, double-blind trials
Authors: Christina Reith, Colin Baigent, Lisa Blackwell, Jonathan Emberson, Enti Spata, Kelly Davies, Heather Halls, Lisa Holland, Kate Wilson, Jane Armitage, Charlie Harper, David Preiss, Alistair Roddick, Anthony Keech, John Simes, Rory Collins, Elizabeth Barnes, Jordan Fulcher, William G Herrington, Adrienne Kirby, Borislava Mihaylova, Rachel O'Connell, Pierre Amarenco, Philip Barter, D John Betteridge (deceased), Michael Blazing, Jackie Bosch, Louise Bowman, Eugene Braunwald, Christopher P Cannon, Michael Clearfield, Stuart Cobbe, Helen M Colhoun, Björn Dahlöf, Barry Davis, James de Lemos, John R Downs, Paul N Durrington, Bengt Fellström, Ian Ford, Maria Grazia Franzosi, John Fuller (deceased), Curt Furberg, Robert Glynn, David Gordon, Antonio Gotto Jr, Richard Grimm, Ajay Gupta, C Morton Hawkins, Graham A Hitman, Hallvard Holdaas (deceased), Alan Jardine, J Wouter Jukema, John JP Kastelein, Sharon Kean, John Kjekshus, Genell Knatterud (deceased), Robert H Knopp (deceased), Wolfgang Koenig, Michael Koren, Vera Krane, Martin Landray, John LaRosa, Roberto Latini, Eva Lonn, Donata Lucci, Jean MacFadyen, Peter Macfarlane, Stephen MacMahon, Aldo Maggioni, Roberto Marchioli, Ian Marschner, Lemuel Moyé, Sabina Murphy, Andrew Neil, Enrico B Nicolis, Chris Packard, Sarah Parish, Terje R Pedersen, Richard Peto, Marc Pfeffer, Neil Poulter, Sara Pressel, Jeffrey Probstfield, Mahboob Rahman, Paul M Ridker, Michele Robertson, Frank Sacks, Naveed Sattar, Roland Schmieder, Patrick W Serruys, Peter Sever, John Shaw (deceased), James Shepherd (deceased), Lara Simpson, Peter Sleight (deceased), Luigi Tavazzi, Gianni Tognoni, Andrew Tonkin, Stella Trompet, Christoph Wanner, Hans Wedel, Stephen Weis, K Michael Welch, Harvey White, John Wikstrand, Lars Wilhelmsen, Stephen Wiviott, Robin Young, Salim Yusuf, Faiez Zannad, Hiroyuki Arashi, Robert Byington, Robert Clarke, Marcus Flather, Uri Goldbourt, Shinya Goto, Jemma Hopewell, Kees Hovingh, Patricia Kearney, George Kitas, Connie Newman, Marc S Sabatine, Greg Schwartz, Liam Smeeth, Jonathan Tobert, John Varigos, Junichi Yamaguchi
Journal: The Lancet (2022)
Mammalian Target of Rapamycin Inhibition in Patients With ST-Segment Elevation Myocardial Infarction
Authors: Barbara E. Stähli, Roland Klingenberg, Dik Heg, Mattia Branca, Robert Manka, Ioannis Kapos, Oliver Müggler, Andrea Denegri, Rahel Kesterke, Florence Berger, Julia Stehli, Alessandro Candreva, Arnold von Eckardstein, David Carballo, Christian Hamm, Ulf Landmesser, François Mach, Tiziano Moccetti, Christian Jung, Malte Kelm, Thomas Münzel, Giovanni Pedrazzini, Lorenz Räber, Stephan Windecker, Christian Templin, Christian M. Matter, Thomas F. Lüscher, Frank Ruschitzka
Journal: Journal of the American College of Cardiology (2022)
Sacubitril/Valsartan and Frailty in Patients With Heart Failure and Preserved Ejection Fraction
Authors: Jawad H. Butt, Pooja Dewan, Pardeep S. Jhund, Inder S. Anand, Dan Atar, Junbo Ge, Akshay S. Desai, Luis E. Echeverria, Lars Køber, Carolyn S.P. Lam, Aldo P. Maggioni, Felipe Martinez, Milton Packer, Jean L. Rouleau, David Sim, Dirk J. Van Veldhuisen, Bojan Vrtovec, Faiez Zannad, Michael R. Zile, Jianjian Gong, Martin P. Lefkowitz, Adel R. Rizkala, Scott D. Solomon, John J.V. McMurray
Journal: Journal of the American College of Cardiology (2022)

Frailty is an increasingly common problem, and frail patients are less likely to receive new pharmacologic therapies because the risk-benefit profile is perceived to be less favorable than in nonfrail patients.This study investigated the efficacy of sacubitril/valsartan according to frailty status in 4,796 patients with heart failure with preserved ejection fraction randomized in the PARAGON-HF (Prospective Comparison of ARNI With ARB Global Outcomes in Heart Failure With Preserved Ejection Fraction) trial.Frailty was measured by using the Rockwood cumulative deficit approach. The primary endpoint was total heart failure hospitalizations or cardiovascular death.A frailty index (FI) was calculable in 4,795 patients. In total, 45.2% had class 1 frailty (FI ≤0.210, not frail), 43.5% had class 2 frailty (FI 0.211-0.310, more frail), and 11.4% had class 3 frailty (FI ≥0.311, most frail). There was a graded relationship between FI class and the primary endpoint, with a significantly higher risk associated with greater frailty (class 1: reference; class 2 rate ratio: 2.19 [95% CI: 1.85-2.60]; class 3 rate ratio: 3.29 [95% CI: 2.65-4.09]). The effect of sacubitril/valsartan vs valsartan on the primary endpoint from lowest to highest FI class (as a rate ratio) was: 0.98 [95% CI: 0.76-1.27], 0.92 [95% CI: 0.76-1.12], and 0.69 [95% CI: 0.51-0.95]), respectively (Pinteraction = 0.23). When FI was examined as a continuous variable, the interaction with treatment was significant for the primary outcome (Pinteraction = 0.002) and total heart failure hospitalizations (Pinteraction < 0.001), with those most frail deriving greater benefit.Frailty was common in heart failure with preserved ejection fraction and associated with worse outcomes. Compared with valsartan, sacubitril/valsartan seemed to show a greater reduction in the primary endpoint with increasing frailty, although this was not significant when FI was examined as a categorical variable. (Prospective Comparison of ARNI With ARB Global Outcomes in Heart Failure With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711).